H. pylori resistance to antibiotics is a growing problem. Clarithromycin resistance occurs via point mutations and decreases the efficacy of standard triple therapy by 66%. Sequential therapy and bismuth-based quadruple therapy are recommended alternatives with success rates over 70%. Levofloxacin resistance is also emerging, though data is limited. Screening for clarithromycin resistance is advised if prevalence is over 20%. Reinfection can occur but is less than 14% after one year. Vaccines show promise but challenges remain developing effective options.

1. H pylori Resistance
Ahmed Alwassief, MD

3. Pathogenesis: Colonization versus
Infection
• Present exclusively in humans since the beginning
• Roughly 50% of the world’s population has HP
• Only 20% of this 50% will ever have any HP
associated condition
• Linked to several disease processes
• Also inversely associated with some disease
processes
• Is/was there some evolutionary advantage to our
relationship?

4. Practice Challenges
• Guidelines vague and variable
• Specialists often reluctant to manage
• Patient questions difficult to answer
• What is the acceptable rate of Tx failure??
>>>> 20%

5. Health Impact
• Ulcers: 80-95% DU and 70-80% GU
• 80% of Gastric cancers. 6X risk for carrier.
• 3-4X risk of NSAID gastropathy.
• Gastric B-cell Lymphoma (“MALT”)
• Non-Ulcer Dyspepsia
• More suspected -
vascular/migraine/autoimmune
• Colon and Pancreatic cancers?

6. Transmission
• Fecal-Oral
• Oral-Oral/ Dental Plaque/Kissing
• Environmental reservoirs (water/fish?)
• Iatrogenic
• Family contacts
• Still poorly understood

7. • Formerly Campylobacter
• Ulcer link 1982 by
Australians J. Robin Warren
(Pathologist), and Barry
Marshall, MD.
• Marshall dramatically
demonstrated Koch’s
postulates by voluntary
ingestion. Reportedly took
more than two years to
clear, trying numerous
treatment regimens,.
• Not accepted as cause of
ulcers until 1994.

8. HP resistance
• Decline in efficacy has been noted with
standard triple therapy over the past 10
years.
• Newer Drugs have a higher eradication rate ,
however, it is likely that it will show similar
phenomenon.
• Since the evolution of drug resistance will
remain a problem, newer therapies must be
implemented sooner rather than later.

11. Clarithromycin Resistance
• There are essentially three point mutations, which
can occur at the positions 2142 (A2142G and
A2142C) and 2143 (A2143G) I
• these mutations resulted in:
• Decrease in binding of the drug.
• No impact on bacterial Viability
• Decreased efficacy of triple therapy by 66.2%
• Problem can be induced by any type of Macrolid

12. levofloxacin Resistance
• More extensive loci
• No enough evidence
• Response rate is 60%

13. Diagnosis of CLA resistance
• Start screening if prevalence is > 20 %
1- The standard methods using culture and
antimicrobial susceptibility testing (e.g. Etest, AB
bioMerieux, Solna, Sweden) take several days
2- Rapid molecular methods including
 standard polymerase chain reaction (PCR)
(Seeflex®ClaR H. pylori ACE detection, Seegene,
Seoul, South Korea)
 Real-time PCR (Engenetix, Vienna, Austria)
 fluorescence in situ hybridization (seaFAST H. pylori)

14. Management
Sequential treatment
• Sequential treatment =(PPI) and amoxicillin for
5 days followed by a PPI t >>>> clarithromycin
and metronidazole for the next 5 days
• In resistant strain standard Tx 32% vs 72%
Seqential Tx
• Theory of success that 1st phase Tx decrease
bacterial load including resistant strains
allowing better result with 2nd phase

15. Management
Bismuth-based quadruple therapy
OBMT
• PPI + Bithmus salt + Metro 250 QID + Tetra 250 QID
• Rational
1. Bismuth salts mechanism of action is not known but appears to be more
like an antiseptic than an antibiotic, and no resistance has been described;
2. Tetracycline is an antibiotic for which resistance is rarely encountered. The
reason is that to reach a high level resistance, three adjacent point
mutations are required which is rare to find in the same organism
3. Metronidazole, resistance is of low clinical impact that can be overcomed
by increasing the dose and duration of treatment >>> only 14% decrease
in treatment success
4. BMT three-in-one capsule (Pylera®) is commercially available
Concern
High doses of bismuth salts were associated with encephalopathy with reports
of fatality

16. Management
Salvage therapy
• Esomeprazole 20 mg BID + amoxicillin 500
mg BID + levofloxacin 500 mg BID.
• Success as a second line Tx is around 75%

17. H Pylori Reinfection
• Reappearance of H. pylori is thought to occur via two distinct
mechanisms, recrudescence and re-infection. Recrudescence reflects
reappearance of the original strain of H. pylori following its temporary
suppression rather than successful eradication. True re-infection
occurs when, after successful eradication,
• Most reinfections in the 1st year post Tx
• Variable incidence world wide and look linked to the local H pylori
Incidence 1-20%
• Comparison of strains of H. pylori following reappearance have shown
that 38% are identical to the pre-treatment strain in the first 6 months
and none are identical following 1 year.
• Recurrence rate is less for 2nd line drugs
• USA 1%
• Iran 20%

18. Vaccine
• Difficulties include HP immune evasive
mechanisms as it involves T Reg recruitment
and down regulation of immune system.
• Recent breakthrough as the protective H.
pylori-derived antigens have already been
administered to humans and have proven
their safety and immunogenicity
• Experimental H. pylori vaccination is under
trial EpiVax “Phase I”

19. Who to test?
• Established
• PUD
• Gastric low-grade MALT lymphoma
• Univestigated dyspepsia
• After endoscopic resection of early cancer
• Evaluate success of eradication therapy
• Controversial
• High Risk for Gastric Ca (e.g. relatives of patients who have gastric cancer)
• Unexplained Iron Deficiency anemia
• Nonulcer dyspepsia
• Chronic nonsteroidal anti-inflammatory drug/aspirin therapy a
• Chronic antisecretory drug therapy (eg, gastroesophageal reflux disease) b
• Relatives of patients who have Hpylori infection
• Patient desires to be tested
• When planning long-term NSAID therapy
• When planning long-term antisecretory therapy.